tbuckley/cabot-search huggingface dataset:
Patterns of tobacco use in low and middle income countries by tobacco product and sociodemographic characteristics: nationally representative survey data from 82 countries
Authors: Michaela Theilmann, Julia M Lemp, Volker Winkler, Jennifer Manne-Goehler, Maja E. Marcus, Charlotte Probst, William A Lopez-Arboleda, Cara Ebert, Christian Bommer, Maya Mathur, Glennis Andall-Brereton, Silver K Bahendeka, Pascal Bovet, Farshad Farzadfar, Erfan Ghasemi, Mary T Mayige, Sahar Saeedi Moghaddam, Kibachio J Mwangi, Shohreh Naderimagham, Lela Sturua, Rifat Atun, Justine I Davies, Till Bärnighausen, Sebastian Vollmer, Pascal Geldsetzer
Journal: BMJ (2022)

To determine the prevalence and frequency of using any tobacco product and each of a detailed set of tobacco products, how tobacco use and frequency of use vary across countries, world regions, and World Bank country income groups, and the socioeconomic and demographic gradients of tobacco use and frequency of use within countries.
Impact of Artificial Intelligence on Colonoscopy Surveillance After Polyp Removal: A Pooled Analysis of Randomized Trials
Authors: Yuichi Mori, Pu Wang, Magnus Løberg, Masashi Misawa, Alessandro Repici, Marco Spadaccini, Loredana Correale, Giulio Antonelli, Honggang Yu, Dexin Gong, Misaki Ishiyama, Shin-ei Kudo, Shunsuke Kamba, Kazuki Sumiyama, Yutaka Saito, Haruo Nishino, Peixi Liu, Jeremy R. Glissen Brown, Nabil M. Mansour, Seth A. Gross, Mette Kalager, Michael Bretthauer, Douglas K. Rex, Prateek Sharma, Tyler M. Berzin, Cesare Hassan
Journal: Clinical Gastroenterology and Hepatology (2022)

Artificial intelligence (AI) tools aimed at improving polyp detection have been shown to increase the adenoma detection rate during colonoscopy. However, it is unknown how increased polyp detection rates by AI affect the burden of patient surveillance after polyp removal.We conducted a pooled analysis of 9 randomized controlled trials (5 in China, 2 in Italy, 1 in Japan, and 1 in the United States) comparing colonoscopy with or without AI detection aids. The primary outcome was the proportion of patients recommended to undergo intensive surveillance (ie, 3-year interval). We analyzed intervals for AI and non-AI colonoscopies for the U.S. and European recommendations separately. We estimated proportions by calculating relative risks using the Mantel-Haenszel method.A total of 5796 patients (51% male, mean 53 years of age) were included; 2894 underwent AI-assisted colonoscopy and 2902 non-AI colonoscopy. When following U.S. guidelines, the proportion of patients recommended intensive surveillance increased from 8.4% (95% CI, 7.4%-9.5%) in the non-AI group to 11.3% (95% CI, 10.2%-12.6%) in the AI group (absolute difference, 2.9% [95% CI, 1.4%-4.4%]; risk ratio, 1.35 [95% CI, 1.16-1.57]). When following European guidelines, it increased from 6.1% (95% CI, 5.3%-7.0%) to 7.4% (95% CI, 6.5%-8.4%) (absolute difference, 1.3% [95% CI, 0.01%-2.6%]; risk ratio, 1.22 [95% CI, 1.01-1.47]).The use of AI during colonoscopy increased the proportion of patients requiring intensive colonoscopy surveillance by approximately 35% in the United States and 20% in Europe (absolute increases of 2.9% and 1.3%, respectively). While this may contribute to improved cancer prevention, it significantly adds patient burden and healthcare costs.
Cellular nanovesicles for therapeutic immunomodulation: A perspective on engineering strategies and new advances
Authors: Endong Zhang, Philana Phan, Zongmin Zhao
Journal: Acta Pharmaceutica Sinica B (2022)

Cellular nanovesicles which are referred to as cell-derived, nanosized lipid bilayer structures, have emerged as a promising platform for regulating immune responses. Owing to their outstanding advantages such as high biocompatibility, prominent structural stability, and high loading capacity, cellular nanovesicles are suitable for delivering various immunomodulatory molecules, such as small molecules, nucleic acids, peptides, and proteins. Immunomodulation induced by cellular nanovesicles has been exploited to modulate immune cell behaviors, which is considered as a novel cell-free immunotherapeutic strategy for the prevention and treatment of diverse diseases. Here we review emerging concepts and new advances in leveraging cellular nanovesicles to activate or suppress immune responses, with the aim to explicate their applications for immunomodulation. We overview the general considerations and principles for the design of engineered cellular nanovesicles with tailored immunomodulatory activities. We also discuss new advances in engineering cellular nanovesicles as immunotherapies for treating major diseases.
The Role of Off-Therapy Viral Kinetics in the Timing and Severity of Flares in Hepatitis B e Antigen–Negative Patients
Authors: Yen-Chun Liu, Wen-Juei Jeng, Chien-Wei Peng, Rong-Nan Chien, Yun-Fan Liaw
Journal: Clinical Gastroenterology and Hepatology (2022)
Ventricular arrhythmias in acute myocardial ischaemia—Focus on the ageing and sex
Authors: Marta Oknińska, Michał Mączewski, Urszula Mackiewicz
Journal: Ageing Research Reviews (2022)

Annually, approximately 17 million people die from cardiovascular diseases worldwide, half of them suddenly. The most common direct cause of sudden cardiac death is ventricular arrhythmia triggered by an acute coronary syndrome (ACS). The study summarizes the knowledge of the mechanisms of arrhythmia onset during ACS in humans and in animal models and factors that may influence the susceptibility to life-threatening arrhythmias during ACS with particular focus on the age and sex. The real impact of age and sex on the arrhythmic susceptibility within the setting of acute ischaemia is masked by the fact that ACSs result from coronary artery disease appearing with age much earlier among men than among women. However, results of researches show that in ageing process changes with potential pro-arrhythmic significance, such as increased fibrosis, cardiomyocyte hypertrophy, decrease number of gap junction channels, disturbances of the intracellular Ca2+ signalling or changes in electrophysiological parameters, occur independently of the development of cardiovascular diseases and are more severe in male individuals. A review of the literature also indicates a marked paucity of research in this area in female and elderly individuals. Greater awareness of sex differences in the aging process could help in the development of personalized prevention methods targeting potential pro-arrhythmic factors in patients of both sexes to reduce mortality during the acute phase of myocardial infarction. This is especially important in an era of aging populations in which women will predominate due to their longer lifespan.
Influence of genetic and cardiometabolic risk factors in Alzheimer’s disease
Authors: Giuseppe Pasqualetti, Tony Thayanandan, Paul Edison
Journal: Ageing Research Reviews (2022)

Alzheimer's disease (AD) is a multifactorial neurodegenerative disorder. Cardiometabolic and genetic risk factors play an important role in the trajectory of AD. Cardiometabolic risk factors including diabetes, mid-life obesity, mid-life hypertension and elevated cholesterol have been linked with cognitive decline in AD subjects. These potential risk factors associated with cerebral metabolic changes which fuel AD pathogenesis have been suggested to be the reason for the disappointing clinical trial results. In appreciation of the risks involved, using search engines such as PubMed, Scopus, MEDLINE and Google Scholar, a relevant literature search on cardiometabolic and genetic risk factors in AD was conducted. We discuss the role of genetic as well as established cardiovascular risk factors in the neuropathology of AD. Moreover, we show new evidence of genetic interaction between several genes potentially involved in different pathways related to both neurodegenerative process and cardiovascular damage.
Healthcare utilization and maternal and child mortality during the COVID-19 pandemic in 18 low- and middle-income countries: An interrupted time-series analysis with mathematical modeling of administrative data
Authors: Tashrik Ahmed, Timothy Roberton, Petra Vergeer, Peter M. Hansen, Michael A. Peters, Anthony Adofo Ofosu, Charles Mwansambo, Charles Nzelu, Chea Sanford Wesseh, Francis Smart, Jean Patrick Alfred, Mamoutou Diabate, Martina Baye, Mohamed Lamine Yansane, Naod Wendrad, Nur Ali Mohamud, Paul Mbaka, Sylvain Yuma, Youssoupha Ndiaye, Husnia Sadat, Helal Uddin, Helen Kiarie, Raharison Tsihory, George Mwinnyaa, Jean de Dieu Rusatira, Pablo Amor Fernandez, Pierre Muhoza, Prativa Baral, Salomé Drouard, Tawab Hashemi, Jed Friedman, Gil Shapira
Journal: PLoS Medicine (2022)

The Coronavirus Disease 2019 (COVID-19) pandemic has had wide-reaching direct and indirect impacts on population health. In low- and middle-income countries, these impacts can halt progress toward reducing maternal and child mortality. This study estimates changes in health services utilization during the pandemic and the associated consequences for maternal, neonatal, and child mortality.
Epigenetics, Harm, and Identity
Authors: Joona Räsänen, Anna Smajdor
Journal: The American Journal of Bioethics (2022)

Robert Sparrow (forthcoming) argues that genome editing is unlikely to be person-affecting for the foreseeable future and, as a result, will neither benefit nor harm edited individuals.We regard Sparrow's claim as being plausibleup to a certain point.However, Sparrow overlooks the role of epigenetics when it comes to determining our identity.Gene editing, as Sparrow suggests, would likely involve complex intervention, either at the gamete stage, or at the blastocyst stage.Since gene editing may result in 'mosaicism', where the amended genes are only active in a subset of the embryo's cells, anything that focuses on one individual embryo would be fraught with uncertainty.It is currently very difficult if not impossible to control and predict the degree to which the change will permeate the organism.Also, in practice, in order to check the accuracy of the editing, genome editing will involve creation of, and selection from amongst, multiple embryos.These are some of the reasons Sparrow suggests genome editing is unlikely to be personaffecting.In all these regards, we suggest that his argument is compelling.Nevertheless, in his treatment of identity and the way it relates to questions about gene editing, the picture is considerably more complex than even Sparrow recognizes.Environmental factors, including our own behavior, and the behaviour of our parents, can cause changes that affect the way our genes work (Hens 2017).If genes are an important aspect of our identity, epigenetic changes, as they are called, are also important; perhaps even more so, since they determine which of our genes are actually expressed.Therefore, epigenetics must also be taken into account when considering whether certain medical interventions harm or benefit specific individuals.Since Parfit (1984) wrote about the non-identity problem, it has been widely accepted by many bioethicists that the essence of identity lies in the genes of the resulting offspring.It is this that makes it true that when Jane chooses to postpone having her child until she is cured of syphilis, she does not benefit that child, but gives birth to a different child.The egg and sperm that create the offspring are different in each case, therefore the child is genetically distinct from whatever child Jane might have had if she hadn't waited.If identity is, as is commonly held, essentially connected with genes, then any intervention that alters genes raises the question of identity.Sparrow claims that bioethicists have assumed that genetic intervention would be person-affecting (rather than identity changing).Yet it seems strange that this should be the case.After all, if our focus is on genes, it would seem to
A novel anti-PD-L1/IL-15 immunocytokine overcomes resistance to PD-L1 blockade and elicits potent antitumor immunity
Authors: Wenqiang Shi, Liangyin Lv, Nan Liu, Hui Wang, Yang Wang, Wen Zhu, Zexin Liu, Jianwei Zhu, Huili Lu
Journal: Molecular Therapy (2022)

Despite the demonstrated immense potential of immune checkpoint inhibitors in various types of cancers, only a minority of patients respond to these therapies. Immunocytokines designed to deliver an immune-activating cytokine directly to the immunosuppressive tumor microenvironment (TME) and block the immune checkpoint simultaneously may provide a strategic advantage over the combination of two single agents. To increase the response rate to checkpoint blockade, in this study, we developed a novel immunocytokine (LH01) composed of the antibody against programmed death-ligand 1 (PD-L1) fused to interleukin (IL)-15 receptor alpha-sushi domain/IL-15 complex. We demonstrate that LH01 efficiently binds mouse or human PD-L1 and maintains IL-15 stimulatory activity. In syngeneic mouse models, LH01 showed improved antitumor efficacy and safety versus anti-PD-L1 plus LH02 (Fc-sushi-IL15) combination and overcame resistance to anti-PD-L1 treatment. Mechanistically, the dual anti-immunosuppressive function of LH01 activated both the innate and adaptive immune responses and induced a favorable and immunostimulatory TME. Furthermore, combination therapy with LH01 and bevacizumab exerts synergistic antitumor effects in an HT29 colorectal xenograft model. Collectively, our results provide supporting evidence that fusion of anti-PD-L1 and IL-15 might be a potent strategy to treat patients with cold tumors or resistance to checkpoint blockade. Despite the demonstrated immense potential of immune checkpoint inhibitors in various types of cancers, only a minority of patients respond to these therapies. Immunocytokines designed to deliver an immune-activating cytokine directly to the immunosuppressive tumor microenvironment (TME) and block the immune checkpoint simultaneously may provide a strategic advantage over the combination of two single agents. To increase the response rate to checkpoint blockade, in this study, we developed a novel immunocytokine (LH01) composed of the antibody against programmed death-ligand 1 (PD-L1) fused to interleukin (IL)-15 receptor alpha-sushi domain/IL-15 complex. We demonstrate that LH01 efficiently binds mouse or human PD-L1 and maintains IL-15 stimulatory activity. In syngeneic mouse models, LH01 showed improved antitumor efficacy and safety versus anti-PD-L1 plus LH02 (Fc-sushi-IL15) combination and overcame resistance to anti-PD-L1 treatment. Mechanistically, the dual anti-immunosuppressive function of LH01 activated both the innate and adaptive immune responses and induced a favorable and immunostimulatory TME. Furthermore, combination therapy with LH01 and bevacizumab exerts synergistic antitumor effects in an HT29 colorectal xenograft model. Collectively, our results provide supporting evidence that fusion of anti-PD-L1 and IL-15 might be a potent strategy to treat patients with cold tumors or resistance to checkpoint blockade.
Leveraging big data of immune checkpoint blockade response identifies novel potential targets
Authors: Y. Bareche, D. Kelly, F. Abbas-Aghababazadeh, M. Nakano, P.N. Esfahani, D. Tkachuk, H. Mohammad, R. Samstein, C.-H. Lee, L.G.T. Morris, P.L. Bedard, B. Haibe-Kains, J. Stagg
Journal: Annals of Oncology (2022)
Uncertainty-aware report generation for chest X-rays by variational topic inference
Authors: Ivona Najdenkoska, Xiantong Zhen, Marcel Worring, Ling Shao
Journal: Medical Image Analysis (2022)

Automating report generation for medical imaging promises to minimize labor and aid diagnosis in clinical practice. Deep learning algorithms have recently been shown to be capable of captioning natural photos. However, doing a similar thing for medical data, is difficult due to the variety in reports written by different radiologists with fluctuating levels of knowledge and experience. Current methods for automatic report generation tend to merely copy one of the training samples in the created report. To tackle this issue, we propose variational topic inference, a probabilistic approach for automatic chest X-ray report generation. Specifically, we introduce a probabilistic latent variable model where a latent variable defines a single topic. The topics are inferred in a conditional variational inference framework by aligning vision and language modalities in a latent space, with each topic governing the generation of one sentence in the report. We further adopt a visual attention module that enables the model to attend to different locations in the image while generating the descriptions. We conduct extensive experiments on two benchmarks, namely Indiana U. Chest X-rays and MIMIC-CXR. The results demonstrate that our proposed variational topic inference method can generate reports with novel sentence structure, rather than mere copies of reports used in training, while still achieving comparable performance to state-of-the-art methods in terms of standard language generation criteria.
Chromosome-Level Genomes Reveal the Genetic Basis of Descending Dysploidy and Sex Determination in <i>Morus</i> Plants
Authors: Zhongqiang Xia, Xuelei Dai, Wei Fan, Changying Liu, Meirong Zhang, Peipei Bian, Yuping Zhou, Liang Li, Baozhong Zhu, Shuman Liu, Zhengang Li, Xiling Wang, Maode Yu, Zhonghuai Xiang, Yu Jiang, Aichun Zhao
Journal: Genomics Proteomics & Bioinformatics (2022)

Multiple plant lineages have independently evolved sex chromosomes and variable karyotypes to maintain their sessile lifestyles through constant biological innovation. Morus notabilis, a dioecious mulberry species, has the fewest chromosomes among Morus spp., but the genetic basis of sex determination and karyotype evolution in this species has not been identified. In this study, three high-quality genome assemblies were generated for Morus spp. [including dioecious M. notabilis (male and female) and Morus yunnanensis (female)] with genome sizes of 301-329 Mb and were grouped into six pseudochromosomes. Using a combination of genomic approaches, we found that the putative ancestral karyotype of Morus species was close to 14 protochromosomes, and that several chromosome fusion events resulted in descending dysploidy (2n = 2x = 12). We also characterized a ∼ 6.2-Mb sex-determining region on chromosome 3. Four potential male-specific genes, a partially duplicatedDNA helicase gene (named MSDH) and three Ty3_Gypsy long terminal repeat retrotransposons (named MSTG1/2/3), were identified in the Y-linked area and considered to be strong candidate genes for sex determination or differentiation. Population genomic analysis showed that Guangdong accessions in China were genetically similar to Japanese accessions of mulberry. In addition, genomic areas containing selective sweeps that distinguish domesticated mulberry from wild populations in terms of flowering and disease resistance were identified. Our study provides an important genetic resource for sex identification research and molecular breeding in mulberry.
A molecularly integrated amygdalo-fronto-striatal network coordinates flexible learning and memory
Authors: Dan C. Li, Niharika M. Dighe, Britton R. Barbee, Elizabeth G. Pitts, Brik Kochoian, Sarah A. Blumenthal, Janet Figueroa, Traci Leong, Shannon L. Gourley
Journal: Nature Neuroscience (2022)
Postremission cytopenia management in patients with acute myeloid leukemia treated with venetoclax and azacitidine in VIALE‐A
Authors: Keith W. Pratz, Courtney D. DiNardo, Dominik Selleslag, Junmin Li, Kazuhito Yamamoto, Marina Konopleva, Don Stevens, Hagop Kantarjian, Fabiola Traina, Adriano Venditti, Jiri Mayer, Melissa Montez, Huan Jin, Yinghui Duan, Deanna Brackman, Jiuhong Zha, Jalaja Potluri, Michael Werner, Brian A. Jonas
Journal: American Journal of Hematology (2022)

Postremission cytopenia management in patients with
Pathological structural conversion of α-synuclein at the mitochondria induces neuronal toxicity
Authors: Minee L. Choi, Alexandre Chappard, Bhanu P. Singh, Catherine Maclachlan, Margarida Rodrigues, Evgeniya I. Fedotova, Alexey V. Berezhnov, Suman De, Christopher J. Peddie, Dilan Athauda, Gurvir S. Virdi, Weijia Zhang, James R. Evans, Anna I. Wernick, Zeinab Shadman Zanjani, Plamena R. Angelova, Noemi Esteras, Andrey Y. Vinokurov, Katie Morris, Kiani Jeacock, Laura Tosatto, Daniel Little, Paul Gissen, David J. Clarke, Tilo Kunath, Lucy Collinson, David Klenerman, Andrey Y. Abramov, Mathew H. Horrocks, Sonia Gandhi
Journal: Nature Neuroscience (2022)

Abstract Aggregation of alpha-synuclein (α-Syn) drives Parkinson’s disease (PD), although the initial stages of self-assembly and structural conversion have not been directly observed inside neurons. In this study, we tracked the intracellular conformational states of α-Syn using a single-molecule Förster resonance energy transfer (smFRET) biosensor, and we show here that α-Syn converts from a monomeric state into two distinct oligomeric states in neurons in a concentration-dependent and sequence-specific manner. Three-dimensional FRET-correlative light and electron microscopy (FRET-CLEM) revealed that intracellular seeding events occur preferentially on membrane surfaces, especially at mitochondrial membranes. The mitochondrial lipid cardiolipin triggers rapid oligomerization of A53T α-Syn, and cardiolipin is sequestered within aggregating lipid–protein complexes. Mitochondrial aggregates impair complex I activity and increase mitochondrial reactive oxygen species (ROS) generation, which accelerates the oligomerization of A53T α-Syn and causes permeabilization of mitochondrial membranes and cell death. These processes were also observed in induced pluripotent stem cell (iPSC)–derived neurons harboring A53T mutations from patients with PD. Our study highlights a mechanism of de novo α-Syn oligomerization at mitochondrial membranes and subsequent neuronal toxicity.
Aberrant astrocyte protein secretion contributes to altered neuronal development in multiple models of neurodevelopmental disorders
Authors: Alison L. M. Caldwell, Laura Sancho, James Deng, Alexandra Bosworth, Audrey Miglietta, Jolene K. Diedrich, Maxim N. Shokhirev, Nicola J. Allen
Journal: Nature Neuroscience (2022)